Cucumber-Derived Nanovesicles Containing Cucurbitacin B for Non-Small Cell Lung Cancer Therapy

被引:33
作者
Chen, Tingting [1 ,2 ]
Ma, Bingxiang [1 ,2 ]
Lu, Shi [1 ,2 ]
Zeng, Lupeng [1 ,2 ]
Wang, Huaying [1 ,2 ]
Shi, Wanhua [1 ,2 ]
Zhou, Linying [3 ]
Xia, Yaokun [4 ]
Zhang, Xi [1 ]
Zhang, Jing [5 ]
Chen, Jinghua [1 ]
机构
[1] Fujian Med Univ, Sch Pharm, Fuzhou 350108, Fujian, Peoples R China
[2] Fujian Med Univ, Fujian Key Lab Drug Target Discovery & Struct & F, Fuzhou 350108, Fujian, Peoples R China
[3] Fujian Med Univ, Publ Technol Serv Ctr, Electron Microscopy Facil, Fuzhou 350108, Fujian, Peoples R China
[4] Fujian Med Univ, Key Lab, Minist Educ Gastrointestinal Canc, Sch Basic Med Sci, Fuzhou 350108, Fujian, Peoples R China
[5] Fujian Agr & Forestry Univ, Coll Life Sci, Dept Chem Biol, Fuzhou 350002, Fujian, Peoples R China
关键词
ROS; STAT3; cucurbitacin B; anticancer; EXOSOME-LIKE NANOVESICLES; INHIBITING STAT3; APOPTOSIS; NANOPARTICLES; DELIVERY; PROLIFERATION; COMBINATION; DOXORUBICIN;
D O I
10.2147/IJN.S362244
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Purpose: In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo. Methods: Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS). Results: CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo. Conclusion: These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.
引用
收藏
页码:3583 / 3599
页数:17
相关论文
共 56 条
[1]   Interaction of cucurbitacins with human serum albumin: Thermodynamic characteristics and influence on the binding of site specific ligands [J].
Abou-Khalil, Rony ;
Jraij, Alia ;
Magdalou, Jacques ;
Ouaini, Naim ;
Tome, Daniel ;
Greige-Gerges, Helene .
JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, 2009, 95 (03) :189-195
[2]   Encapsulation of cucurbitacin B into lipid polymer hybrid nanocarriers induced apoptosis of MDAMB231 cells through PARP cleavage [J].
Bakar-Ates, Filiz ;
Ozkan, Erva ;
Sengel-Turk, Ceyda Tuba .
INTERNATIONAL JOURNAL OF PHARMACEUTICS, 2020, 586
[3]   Plant Extracellular Vesicles Contain Diverse Small RNA Species and Are Enriched in 10-to 17-Nucleotide "Tiny" RNAs [J].
Baldrich, Patricia ;
Rutter, Brian D. ;
Karimi, Hana Zand ;
Podicheti, Ram ;
Meyers, Blake C. ;
Innes, Roger W. .
PLANT CELL, 2019, 31 (02) :315-324
[4]   Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes [J].
Cai, Qiang ;
Qiao, Lulu ;
Wang, Ming ;
He, Baoye ;
Lin, Feng-Mao ;
Palmquist, Jared ;
Huang, Sienna-Da ;
Jin, Hailing .
SCIENCE, 2018, 360 (6393) :1126-1129
[5]   A folic acid-modified non-viral vector combines gene therapy with chemotherapy to reverse cancer chemotherapy resistance [J].
Chen, Jing ;
Nie, Wen ;
Hu, Yuzhu ;
Shen, Yangmei ;
Lin, Yunzhu ;
Wang, Bilan ;
Qian, Zhiyong ;
Gao, Xiang .
APPLIED MATERIALS TODAY, 2022, 26
[6]   Plant Exosome-like Nanovesicles: Emerging Therapeutics and Drug Delivery Nanoplatforms [J].
Dad, Haseeb Anwar ;
Gu, Ting-Wei ;
Zhu, Ao-Qing ;
Huang, Lu-Qi ;
Peng, Li-Hua .
MOLECULAR THERAPY, 2021, 29 (01) :13-31
[7]   NIR-II Excitation Phototheranostic Nanomedicine for Fluorescence/Photoacoustic Tumor Imaging and Targeted Photothermal-Photonic Thermodynamic Therapy [J].
Dai, Yeneng ;
Zhao, Honghai ;
He, Kun ;
Du, Wenyu ;
Kong, Yingjie ;
Wang, Zhen ;
Li, Meixing ;
Shen, Qingming ;
Sun, Pengfei ;
Fan, Quli .
SMALL, 2021, 17 (42)
[8]   Dual-stimuli-responsive TiOx/DOX nanodrug system for lung cancer synergistic therapy [J].
Dai, Zideng ;
Song, Xue-Zhi ;
Cao, Junkai ;
He, Yunping ;
Wen, Wen ;
Xu, Xinyu ;
Tan, Zhenquan .
RSC ADVANCES, 2018, 8 (39) :21975-21984
[9]   Cucurbitacin B synergistically enhances the apoptosis-inducing effect of arsenic trioxide by inhibiting STAT3 phosphorylation in lymphoma Ramos cells [J].
Ding, Xiuli ;
Chi, Jiadong ;
Yang, Xue ;
Hao, Jian ;
Liu, Chang ;
Zhu, Cuihong ;
Wang, Xiaodong ;
Liu, Xiaohui ;
Niu, Yangyang ;
Ji, Wei ;
Chen, Dan ;
Wu, Xiongzhi .
LEUKEMIA & LYMPHOMA, 2017, 58 (10) :2439-2451
[10]   Chitosan oligosaccharide decorated liposomes combined with TH302 for photodynamic therapy in triple negative breast cancer [J].
Ding, Yinan ;
Yang, Rui ;
Yu, Weiping ;
Hu, Chunmei ;
Zhang, Zhiyuan ;
Liu, Dongfang ;
An, Yanli ;
Wang, Xihui ;
He, Chen ;
Liu, Peidang ;
Tang, Qiusha ;
Chen, Daozhen .
JOURNAL OF NANOBIOTECHNOLOGY, 2021, 19 (01)